Biology subjects

Flaquer, I.

Publications and source records attributed to Flaquer, I..

3 recordsLinked to original sources

bioRxiv2021

A Purkinje cell to parabrachial nucleus pathway enables broad cerebellar influence over the forebrain and emotional valence

In addition to its well-known contributions to motor function, the cerebellum is involved in emotional regulation, anxiety, and affect1-4. We found that suppressing the firing of cerebellar Purkinje cells (PCs) rapidly excites forebrain areas that could contribute to such functions (including the amygdala, basal forebrain, and septum), but that the classic cerebellar outputs, the deep cerebellar nuclei (DCN), do not project to these forebrain regions. Here we show that PCs directly inhibit parabrachial nuclei (PBN) neurons that project to and influence numerous forebrain regions in a manner distinct from the DCN pathway. We also found that the PBN and DCN output pathways differentially influence behavior: suppressing the PC to PBN pathway is aversive and does not affect the speed of movement, whereas suppressing the PC to DCN pathway is not aversive and reduces speed. Molecular profiling shows that PCs inhibit numerous types of PBN neurons that control diverse nonmotor behaviors5-9. Therefore, the PBN pathway allows the cerebellum to regulate activity in many forebrain regions and may be an important substrate for nonmotor disorders related to cerebellar dysfunction.

neuroscience↗

bioRxiv2020

Cerebellar Purkinje cell activity modulates aggressive behavior

Although the cerebellum is traditionally associated with balance and motor function, it also plays wider roles in affective and cognitive behaviors. Evidence suggests that the cerebellar vermis may regulate aggressive behavior, though the cerebellar circuits and patterns of activity that influence aggression remain unclear. We used optogenetic methods to bidirectionally modulate the activity of spatially-delineated cerebellar Purkinje cells to evaluate the impact on aggression in mice. Increasing Purkinje cell activity in the vermis significantly reduced the frequency of attacks in a resident-intruder assay. Reduced aggression was not a consequence of impaired motor function, because optogenetic stimulation did not alter motor performance. In complementary experiments, optogenetic inhibition of Purkinje cells in the vermis increased the frequency of attacks. These results establish Purkinje cell activity in the cerebellar vermis regulates aggression, and further support the importance of the cerebellum in driving affective behaviors that could contribute to neurological disorders.

neuroscience↗

bioRxiv2019

Cerebellum-specific deletion of the GABAA receptor δ subunit alters anxiety-like, social and maternal behaviors without affecting motor performance

GABAA receptors containing the {delta}GABAA subunit ({delta}GABAARs) are involved in many physiological and pathophysiological processes, such as sleep, pain, stress, anxiety-related behaviors, and postpartum depression. These extrasynaptically located, high affinity and slowly desensitizing receptors mediate tonic inhibition throughout the brain, including in granule cells (GCs) of the cerebellar input layer. However, the extent to which {delta}GABAARs control the excitability of the cerebellar input layer and ultimately regulate behavior is unknown. We therefore deleted {delta}GABAA subunits specifically from GCs and determined the behavioral consequences in mice. Deletion reduced tonic inhibition and increased input layer excitability, but remarkably, did not affect either locomotion or motor learning. Unexpectedly, {delta}GABAA deletion heightened anxiety-like behaviors, and caused female-specific alterations in social and maternal behavior. Our findings establish that the cerebellar input layer is critical for regulating diverse behaviors that are relevant to psychiatric and neurodevelopmental disorders but were previously not associated with the cerebellum.

neuroscience↗